13-103052782-G-T

Variant names:

• chr13-103052782-G-T
• rs67736127
• NM_000452.3:c.497-74C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000452.3(SLC10A2):​c.497-74C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 926,222 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (59 hom., cov: 32)
  • Exomes 𝑓: 0.018 (203 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 2 publications found

Genes affected

SLC10A2 (HGNC:10906): (solute carrier family 10 member 2) This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

SLC10A2 Gene-Disease associations (from GenCC):

• bile acid malabsorption, primary, 1

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0246 (3741/152162) while in subpopulation AFR AF = 0.0371 (1540/41534). AF 95% confidence interval is 0.0355. There are 59 homozygotes in GnomAd4. There are 1733 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 59 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.497-74C>A		intron	N/A	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.497-74C>A		intron	N/A	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 152044 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.0183 AC: 14171 AN: 774060 Hom.: 203 AF XY: 0.0180 AC XY: 7400 AN XY: 411432

African (AFR) AF: 0.0393 AC: 783 AN: 19900

American (AMR) AF: 0.00931 AC: 389 AN: 41762

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 1450 AN: 21712

East Asian (EAS) AF: 0.0000276 AC: 1 AN: 36202

South Asian (SAS) AF: 0.00455 AC: 326 AN: 71688

European-Finnish (FIN) AF: 0.0117 AC: 598 AN: 51144

Middle Eastern (MID) AF: 0.0356 AC: 157 AN: 4406

European-Non Finnish (NFE) AF: 0.0197 AC: 9632 AN: 489534

Other (OTH) AF: 0.0221 AC: 835 AN: 37712

GnomAD4 genome AF: 0.0246 AC: 3741 AN: 152162 Hom.: 59 Cov.: 32 AF XY: 0.0233 AC XY: 1733 AN XY: 74382

African (AFR) AF: 0.0371 AC: 1540 AN: 41534

American (AMR) AF: 0.0128 AC: 196 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 255 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00333 AC: 16 AN: 4810

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10590

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0220 AC: 1498 AN: 67994

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0232 Hom.: 70

Bravo AF: 0.0251

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67736127; hg19: chr13-103705132;